Improving the efficacy of late-line immunotherapy for advanced esophageal cancer: the addition of local radiotherapy

Background: The advent of immunotherapy has significantly revolutionized therapies for advanced esophageal cancer (EC). However, clinical data on combining immune checkpoint inhibitors (ICIs) and radiotherapy (RT) in advanced EC remain insufficient. Objectives: This study aimed to evaluate the effectiveness and safety of combining immunotherapy and radiation as a second or subsequent line of treatment for advanced EC. Design and methods: We retrospectively analyzed patients with advanced EC who received late-line ICIs and categorized them into two subgroups based on whether they received RT. The differences in survival and adverse events (AEs) were evaluated. Inverse probability of treatment weighting (IPTW) and 1:1 propensity-score matching (PSM) analysis were used to minimize confounding. Results: The analysis included data from 131 patients. The median progression-free survival (mPFS) was 9.1 months in the RT group, compared to 4.3 months in the non-radiotherapy (NRT) group ( p = 0.0087). The median overall survival (mOS) was 13.5 months in the RT group, which is longer than the 7.3 months in the NRT group ( p = 0.014). IPTW and 1:1 PSM analysis also showed that the RT group has longer mOS and mPFS. Among them, a higher biologically effective dose (BED) was associated with better survival than the lower dose group (16.1 months vs 10.2 months, p = 0.048). RT was an independent factor of better overall survival and progression-free survival in multivariable analysis, regardless of whether IPTW was used. For any grade of AE, any grade neutropenia (60.7% vs 41.4%, p = 0.028) and esophagitis (21.3% vs 1.4%, p < 0.001) were more common in the RT group. However, the incidence of grade 3–4 AEs did not differ significantly. Conclusion: Adding RT to second-line or later immunotherapy regimens for EC correlates with enhanced survival outcomes and manageable toxicity.